This proposal, designed to investigate basic immune mechanisms in the human lung, focuses on Immunoglobulin G as a pivotal molecule in host defense of the lower respiratory tract. We are characterizing its function in terms of activity in the four respective (gamma) chain subclasses. Three lung mechanisms that directly involve specific gamma-chain function are being emphasized: 1) development of opsonic antibody, 2) specific subclass binding to alveolar macrophages which promotes phagocytosis and 3) following phagocytosis, release of chemotactic substances from macrophages which may initiate the inflammatory process in lung parenchyma. The pattern of IgG subclasses present in respiratory secretions (bronchoalveolar lavage) and serum will be identified for a variety of interstitial lung diseases which have elevated concentrations of IgG in lung secretions or tissue. During the second year of this project (4/7/79-3/31/80) we have accomplished the following: 1) Precipitating antisera have been prepared against the four gamma-chain subclasses; 2) At least two chemotactic molecules secreted by alveolar macrophages have been isolated and in part characterized; 3) Antigen specific (Immunotype 4 Pseudomonas aeruginosa) IgG opsonic antibody has been isolated; and 4) IgG and other immunoglobulins (IgE, IgA) have been quantitated in the lung lavage fluid and serum of a large number of normal humans and patients with primary lung cancer. Observations on patients with diffuse interstitial lung diseases have continued as well. About 70 percent of patients with IPF have collagenase in lung lavage fluid; this finding seems specific for this diffuse interstitial lung disease.